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OBJECTIVES: Metabolic dysfunction-associated fatty liver disease (MAFLD), a globally prevalent disease, is closely linked to insulin resistance (IR). Physical activity (PA) is closely linked to both MAFLD and IR. We aim to explore the dose-response relationship between metabolic score for IR (METS-IR)/homeostasis model assessment of IR (HOMA-IR) and MAFLD, and investigate the relationship between PA, IR and MAFLD. METHODS: Participants from the NHANES study were included in this cross-section study. Logistic regression and the receiver operating characteristic were used to assess the predictive performance of METS-IR/HOMA-IR for MAFLD. Restrictive cubic splines were performed to visualize their dose-response relationship. Decision tree analysis was used to identify high-risk populations of MAFLD. PA's mediating effect in the association between METS-IR/HOMA-IR and MAFLD was also examined. RESULTS: Of all 1,313 participants, 693 had MAFLD (52.78%). There were a positive association between METS-IR (OR = 1.162, 95% CI = 1.126-1.199) and HOMA-IR (OR = 1.630, 95% CI = 1.431-1.856) and MAFLD risk. The AUCs of the METS-IR and HOMA-IR were 0.831 (0.809, 0.853) and 0.767 (0.741, 0.791), respectively, with significantly different predictive performance (P < 0.001). Adding METS-IR/HOMA-IR to the basic model greatly improved the statistical significance for MAFLD. Five high-risk subgroups were identified for MAFLD. PA mediated about 0.81% and 0.78% (indirect effect/total effect) in the association between METS-IR/HOMA-IR and MAFLD. CONCLUSIONS: MAFLD risk might be predicted by METS-IR/HOMA-IR, among which METS-IR performed better. And PA mediated the association between them. More attention should be paid to the therapeutic effect of lifestyle changes on MAFLD. HIGHLIGHTS: 1. Positive associations were found between METS-IR and HOMA-IR and MAFLD risk. 2. METS-IR has better predictive performance for MAFLD risk than HOMA-IR. 3.Two high-risk subgroups were identified for MAFLD by METS-IR: individuals with METS-IR ≥ 40; Hispanic black individuals with 34 ≤ METS-IR < 40 and aged ≥ 46. 4. In the significant association between METS-IR/HOMA-IR and MAFLD, about 0.81% and 0.78% (indirect effect/total effect), respectively, were mediated by physical activity.
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Ejercicio Físico , Resistencia a la Insulina , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Estados Unidos/epidemiología , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Encuestas Nutricionales , Pronóstico , Factores de RiesgoRESUMEN
Objective: Mahuang Guizhi Decoction (MGD), an essential herbal pair in traditional Chinese medicine, is able to release cold, fever and asthma, mainly containing alkaloids, flavonoids, phenylpropanoids and amino acids. However, the absorption and distribution of these four category compounds in vivo still remained unclearly. Methods: In our research, we utilized UPLC-Q-TOF-MS technique to identify the constituents within MGD, as well as the prototypes of MGD and their metabolites absorbed in plasma and brain. We further profiled the drug-time curve of prototypes and metabolites of MGD both in plasma and brain. Results: Our results showed that 105 constituents were characterized in MGD. Thirty of them could be absorbed into blood, and ten of them could be distributed into brain. We also discovered eight new bio-transformed metabolites in blood, and a half of which could pass through the blood-brain barrier. In addition, all components detected in vivo could be absorbed and distributed immediately. Conclusion: These findings provide an approachable method to analyze the potential bio-active compounds in MGD and their in vivo behaviors, which could promote the efficacious material basis study of MGD and the security of clinical utilization.
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The transient surface current density reflects the external coupling of the electromagnetic pulse (EMP) to the tested device. In this paper, the generation mechanism and measurement principle of conductor surface current density are introduced, and the surface current density distribution irradiated by EMP on a typical aircraft structure is simulated and analyzed. The traditional surface current density is usually measured by B-dot antenna, but its output signal is the differential of the measured signal, so additional integrators or numerical integration of the measured data are required. In this paper, a self-integrating surface current sensor based on optical fiber transmission is designed based on the shielded loop antenna with gap structure. The output signal is the real signal waveform to be measured. Compared with coaxial cables, integrated optical fiber transmission improves the anti-interference ability of long-distance transmission signals. At the same time, the design process of the sensor is introduced in detail. The bandwidth of the sensor is 300 kHz~500 MHz, the sensitivity is calibrated at 1.23 (A·m-1)/mV, and the dynamic range is ±25~1400 A·m-1 (35 dB). The surface current of a metal plate is measured in a bounded wave electromagnetic pulse simulator using a detector developed in this paper. The test results show that the developed sensor has good engineering applicability.
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Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has become the most common chronic liver disease worldwide. We aimed to explore the gender-related association between nine indexes (BMI/WC/VAI/LAP/WHtR/TyG/TyG-BMI/TyG-WC/TyG-WHtR) and MAFLD/NAFLD and examine their diagnostic utility for these conditions. Methods: Eligible participants were screened from the 2017-2018 cycle data of National Health and Nutrition Examination Survey (NHANES). Logistic regression and receiver operating characteristic (ROC) curve were used to assess the predictive performance of 9 indexes for MAFLD/NAFLD. Results: Among the 809 eligible individuals, 478 had MAFLD and 499 had NAFLD. After adjusting for gender, age, ethnicity, FIPR and education level, positive associations with the risk of MAFLD/NAFLD were found for all the nine indexes. For female, TyG-WHtR presented the best performance in identifying MAFLD/NAFLD, with AUC of 0.845 (95% CI = 0.806-0.879) and 0.831 (95% CI = 0.791-0.867) respectively. For male, TyG-WC presented the best performance in identifying MAFLD/NAFLD, with AUC of 0.900 (95% CI = 0.867-0.927) and 0.855 (95% CI = 0.817-0.888) respectively. Conclusion: BMI/WC/VAI/LAP/WHtR/TyG/TyG-BMI/TyG-WC/TyG-WHtR are important indexes to identify the risk of MAFLD and NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto , Masculino , Femenino , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Transversales , Encuestas Nutricionales , Índice de Masa CorporalRESUMEN
Centronuclear myopathy (CNM) is a congenital neuromuscular disorder caused by pathogenic variation in genes associated with membrane trafficking and excitation-contraction coupling (ECC). Bi-allelic autosomal-recessive mutations in striated muscle enriched protein kinase (SPEG) account for a subset of CNM patients. Previous research has been limited by the perinatal lethality of constitutive Speg knockout mice. Thus, the precise biological role of SPEG in developing skeletal muscle remains unknown. To address this issue, we generated zebrafish spega, spegb and spega;spegb (speg-DKO) mutant lines. We demonstrated that speg-DKO zebrafish faithfully recapitulate multiple phenotypes associated with CNM, including disruption of the ECC machinery, dysregulation of calcium homeostasis during ECC and impairment of muscle performance. Taking advantage of zebrafish models of multiple CNM genetic subtypes, we compared novel and known disease markers in speg-DKO with mtm1-KO and DNM2-S619L transgenic zebrafish. We observed Desmin accumulation common to all CNM subtypes, and Dnm2 upregulation in muscle of both speg-DKO and mtm1-KO zebrafish. In all, we establish a new model of SPEG-related CNM, and identify abnormalities in this model suitable for defining disease pathomechanisms and evaluating potential therapies. This article has an associated First Person interview with the joint first authors of the paper.
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Miopatías Estructurales Congénitas , Pez Cebra , Animales , Dinamina II/genética , Dinamina II/metabolismo , Humanos , Ratones , Proteínas Musculares/metabolismo , Músculo Esquelético/patología , Mutación , Miopatías Estructurales Congénitas/genética , Miopatías Estructurales Congénitas/patología , Quinasa de Cadena Ligera de Miosina/genética , Quinasa de Cadena Ligera de Miosina/metabolismo , Fenotipo , Proteínas Serina-Treonina Quinasas , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
With the randomness and immeasurability properties of zero point, the conventional self-supporting film thickness measurement model must calibrate the distance between two chromatic confocal sensors using a standard part whose thickness needs to be measured by other methods in advance. The measurement performance is easily disturbed by the calibration process, and by the accuracy of sample thickness or its uniformity. In order to overcome these limitations, a new thickness measurement model was developed by adding an auxiliary transparent film in the initial position of the dispersion field. The lower plane of the reference film is not only applied as the zero point of the first sensor but also can be measured by another sensor, whose value is equal to the sensor distance. Theoretical analysis and simulation showed that the proposed method does not change the linear relationship of the displacement coefficient. In order to verify the proposed measurement model, a laboratory thickness measurement system was developed based on two commercial chromatic confocal sensors with a displacement accuracy less than 0.2 µm. A set of self-supporting film was measured using the proposed system, the traditional method, and the reference system. These experiments indicated that the standard deviation of the calibration results of the sensor distance based on the proposed method was reduced to 0.1 µm, which can be concluded that its stability was improved significantly compared to the conventional model. In addition, the proposed method was able to achieve a measurement accuracy of 0.4 µm, which can demonstrate its efficiency and practicability.
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Accurate overlapping-peaks extraction plays a critical role in chromatic confocal thickness measurement of ultra-thin transparent film. However, the current algorithms usually appear as a perceptible extraction error resulting from the disturbing influence among peaks in the process of fitting the spectral axial response signal (sARS) of the two measuring surfaces. In this paper, we propose an adaptive modal decomposition method to extract multi peaks for the ultra-thin materials. With this method, the sARS can be firstly decomposed into several sub-modes, which can be used to obtain the peak wavelength of each measuring surface by the existing single peak extraction algorithms, such as the centroid method and Gauss fitting method. Monte Carlo simulations and experimental tests demonstrate that the proposed algorithm has significant improvements over the existing nonlinear fitting algorithms in terms of peak extraction accuracy and precision.
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Dynamin 2 (DNM2) encodes a ubiquitously expressed large GTPase with membrane fission capabilities that participates in the endocytosis of clathrin-coated vesicles. Heterozygous mutations in DNM2 are associated with two distinct neuromuscular disorders, Charcot-Marie-Tooth disease (CMT) and autosomal dominant centronuclear myopathy (CNM). Despite extensive investigations in cell culture, the role of dynamin 2 in normal muscle development is poorly understood and the consequences of DNM2 mutations at the molecular level in vivo are not known. To address these gaps in knowledge, we developed transgenic zebrafish expressing either wild-type dynamin 2 or dynamin 2 with either a CNM or CMT mutation. Taking advantage of the live imaging capabilities of the zebrafish embryo, we establish the localization of wild-type and mutant dynamin 2 in vivo, showing for the first time distinctive dynamin 2 subcellular compartments. Additionally, we demonstrate that CNM-related DNM2 mutations are associated with protein mislocalization and aggregation. Lastly, we define core phenotypes associated with our transgenic mutant fish, including impaired motor function and altered muscle ultrastructure, making them the ideal platform for drug screening. Overall, using the power of the zebrafish, we establish novel insights into dynamin 2 localization and dynamics and provide the necessary groundwork for future studies examining dynamin 2 pathomechanisms and therapy development.
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Dinamina II/genética , Dinamina II/metabolismo , Mutación , Animales , Animales Modificados Genéticamente , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Modelos Animales de Enfermedad , Endocitosis , Heterocigoto , Humanos , Músculo Esquelético/metabolismo , Enfermedades Neuromusculares/genética , Enfermedades Neuromusculares/metabolismo , Fenotipo , Activación Transcripcional , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Dynamin 2 (DNM2) belongs to a family of large GTPases that are well known for mediating membrane fission by oligomerizing at the neck of membrane invaginations. Autosomal dominant mutations in the ubiquitously expressed DNM2 cause 2 discrete neuromuscular diseases: autosomal dominant centronuclear myopathy (ADCNM) and dominant intermediate Charcot-Marie-Tooth neuropathy (CMT). CNM and CMT mutations may affect DNM2 in distinct manners: CNM mutations may cause protein hyperactivity with elevated GTPase and fission activities, while CMT mutations could impair DNM2 lipid binding and activity. DNM2 is also a modifier of the X-linked and autosomal recessive forms of CNM, as DNM2 protein levels are upregulated in animal models and patient muscle samples. Strikingly, reducing DNM2 has been shown to revert muscle phenotypes in preclinical models of CNM. As DNM2 emerges as the key player in CNM pathogenesis, the role(s) of DNM2 in skeletal muscle remains unclear. This review aims to provide insights into potential pathomechanisms related to DNM2-CNM mutations, and discuss exciting outcomes of current and future therapeutic approaches targeting DNM2 hyperactivity.
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Dinaminas/genética , Mutación/genética , Enfermedades Neuromusculares/genética , Enfermedades Neuromusculares/terapia , Animales , Dinamina II , Humanos , Músculo EsqueléticoRESUMEN
Nanomechanical electron shuttles can work as ratchets for radio-frequency rectification. We develop a full stochastic model of coupled shuttles, where the mechanical motion of nanopillars and the incoherent electronic tunneling are modeled by a Markov chain. In particular, the interaction of their randomness is taken into account, so that a linear master equation is constructed. Numerical solutions from our fast approximate method and analytical derivation reveal the symmetry breaking, which results in the direct current observed in earlier measurements [Phys. Rev. Lett. 105, 067204 (2010)PRLTAO0031-900710.1103/PhysRevLett.105.067204]. Additionally, the method can facilitate device simulation of more complex designs such as shuttle arrays.
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Nemaline myopathy is characterized by muscle weakness and the presence of rod-like (nemaline) bodies. The genetic etiology of nemaline myopathy is becoming increasingly understood with mutations in ten genes now known to cause the disease. Despite this, the mechanism by which skeletal muscle weakness occurs remains elusive, with previous studies showing no correlation between the frequency of nemaline bodies and disease severity. To investigate the formation of nemaline bodies and their role in pathogenesis, we generated overexpression and loss-of-function zebrafish models for skeletal muscle α-actin (ACTA1) and nebulin (NEB). We identify three distinct types of nemaline bodies and visualize their formation in vivo, demonstrating these nemaline bodies not only exhibit different subcellular origins, but also have distinct pathological consequences within the skeletal muscle. One subtype is highly dynamic and upon breakdown leads to the accumulation of cytoplasmic actin contributing to muscle weakness. Examination of a Neb-deficient model suggests this mechanism may be common in nemaline myopathy. Another subtype results from a reduction of actin and forms a more stable cytoplasmic body. In contrast, the final type originates at the Z-disk and is associated with myofibrillar disorganization. Analysis of zebrafish and muscle biopsies from ACTA1 nemaline myopathy patients demonstrates that nemaline bodies also possess a different protein signature. In addition, we show that the ACTA1(D286G) mutation causes impaired actin incorporation and localization in the sarcomere. Together these data provide a novel examination of nemaline body origins and dynamics in vivo and identifies pathological changes that correlate with muscle weakness.
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Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Miopatías Nemalínicas/patología , Miopatías Nemalínicas/fisiopatología , Actinina/genética , Actinina/metabolismo , Actinas/metabolismo , Animales , Animales Modificados Genéticamente , Citoplasma/metabolismo , Citoplasma/patología , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Morfolinos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Debilidad Muscular/patología , Debilidad Muscular/fisiopatología , Mutación , Fenotipo , Sarcómeros/metabolismo , Sarcómeros/patología , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Myofibrillar myopathies are a group of muscle disorders characterized by the disintegration of skeletal muscle fibers and formation of sarcomeric protein aggregates. All the proteins known to be involved in myofibrillar myopathies localize to a region of the sarcomere known as the Z-disk, the site at which defects are first observed. Given the common cellular phenotype observed in this group of disorders, it is thought that there is a common mechanism of pathology. Mutations in filamin C, which has several proposed roles in the development and function of skeletal muscle, can result in filamin-related myofibrillar myopathy. The lack of a suitable animal model system has limited investigation into the mechanism of pathology in this disease and the role of filamin C in muscle development. Here, we characterize stretched out (sot), a zebrafish filamin Cb mutant, together with targeted knockdown of zebrafish filamin Ca, revealing fiber dissolution and formation of protein aggregates strikingly similar to those seen in filamin-related myofibrillar myopathies. Through knockdown of both zebrafish filamin C homologues, we demonstrate that filamin C is not required for fiber specification and that fiber damage is a consequence of muscle activity. The remarkable similarities in the myopathology between our models and filamin-related myofibrillar myopathy makes them suitable for the study of these diseases and provides unique opportunities for the investigation of the function of filamin C in muscle and development of therapies.
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Modelos Animales de Enfermedad , Proteínas de Microfilamentos/genética , Distrofias Musculares/genética , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Tipificación del Cuerpo/genética , Codón sin Sentido , Análisis Mutacional de ADN , Embrión no Mamífero/metabolismo , Embrión no Mamífero/patología , Filaminas , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Ligamiento Genético , Humanos , Funciones de Verosimilitud , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/fisiología , Contracción Muscular , Fibras Musculares de Contracción Lenta/metabolismo , Fibras Musculares de Contracción Lenta/patología , Distrofias Musculares/embriología , Mutagénesis , Miosinas/metabolismo , Fenotipo , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiología , Pez Cebra/embriología , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/fisiologíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the basis of distinctive function of acupoint through observing the effects of acupuncture at the areas of acupoint and non-acupoint on functional connectivity of different brain regions.</p><p><b>METHODS</b>Twenty-one healthy volunteers were randomly divided into two groups: 12 cases in the acupoint group and 9 cases in the non-acupoints group. Bilateral Zusanli (ST 36) and its lateral 3-4 mm were punctured with twirling manipulation in the acupoint group and the non-acupoints group respectively. Before and after 25 minutes treatment, data of functional magnetic resonance imaging (fMRI) scanning was taken from bilateral cingulate gyrus (seed point) to analyze the functional connectivity in both groups.</p><p><b>RESULTS</b>Brain functional connectivity was demonstrated widely in both acupoint group and non-acupoint group after acupuncture. Comparing with the non-acupoint group, in the acupoint group, brain functional connectivity with posterior cingulate gyrus was found more intensively in the bilateral tonsil, right dentate nucleus, bilateral uvula, left declive and right tuber of cerebellum, as well as in the left inferior frontal gyrus, right middle temporal gyurs, bilateral paracentral lobule, left cingulate cortex, right superior temporal gyrus, right anterior cingulate gyrus etc., however, its connectivity was less in the bilateral medial frontal gyrus and right inferior frontal gyrus.</p><p><b>CONCLUSION</b>Both acupoint and non-acupoint can evoke brain functional connectivity that is similar on the most of regions, but the intensity of this connectivity in the acupoint group is higher than that in the non-acupoint group.</p>
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Adulto , Femenino , Humanos , Masculino , Adulto Joven , Acupuntura , Puntos de Acupuntura , Encéfalo , Diagnóstico por Imagen , Fisiología , Mapeo Encefálico , Imagen por Resonancia Magnética , RadiografíaRESUMEN
The materials used to prepare the certified reference materials (CRMs) for Cd rice flour described here were taken from Cd-contaminated rice samples, round-grained and non-sticky rice grown in different provinces throughout China. The Cd rice materials were first blown to remove dust and husk, and then were successively ground, sieved, dried and mixed to form homogeneous rice flour. The Cd rice flour was packed in glass bottles, each bottle containing 40 g. All bottled CRMs were subjected to 60Co radiation (2.5 megarads) for long-term preservation. Atomic absorption spectrometry was used to determine the homogeneity of the cadmium content in each material. The certification of the cadmium content for the three CRMs was performed using isotope dilution mass spectrometry.